A Study of MEDI7352 in Painful Osteoarthritis of the Knee
Primary Purpose
Chronic Pain
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
MEDI7352 for IV infusion
Placebo for IV infusion
MEDI7352 for Subcutaneous Injection
Placebo for Subcutaneous Injection
Sponsored by
About this trial
This is an interventional other trial for Chronic Pain
Eligibility Criteria
Inclusion Criteria:
- Male and female subjects with painful osteoarthritis (OA) of the knee. Female subjects must be postmenopausal or surgically sterile.
- Body weight between 50kg and 145kg
- Willing and able to comply with the requirements of the protocol
Exclusion Criteria:
- Current treatment with another biologic therapeutic agent
- Current of historical diagnosis of RA
- Current diagnosis of an immunological condition that is associated with another form of arthritis in addition to OA, including traumatic arthritis or a seronegative spondyloarthropathy
- At risk of destructive arthropathy, including Rapidly Progressive Osteoarthritis (RPOA), osteonecrosis, spontaneous osteonecrosis of the knee, subchondral insufficiency fractures, hip dislocation and pathological fracture
- Presence of clinically significant neuropathy or other clinically significant disorder involving abnormal peripheral sensation.
- Current serious or unstable clinically important illness.
Sites / Locations
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Arm Label
MEDI7352 IV
IV Placebo
MEDI7352 Subcutaneous Injection
Subcutaneous Placebo
Arm Description
Up to 11 cohorts of subjects are planned to be dosed by IV infusion, with single and multiple ascending doses.
Up to 11 cohorts of subjects are planned to be dosed by IV infusion, with single and multiple ascending doses.
1 cohort of subjects is planned to be dosed by subcutaneous injection, one single ascending dose cohort.
1 cohort of subjects is planned to be dosed by subcutaneous injection, one single ascending dose cohort.
Outcomes
Primary Outcome Measures
Number of Participants with Adverse Events as a Measure of Safety and Tolerability of MEDI7352
Adverse events, serious adverse events,
Number of Participants with Adverse Events as a Measure of Safety and Tolerability of MEDI7352
Clinical laboratory assessments (serum chemistry, hematology, urinalysis)
Number of Participants with Adverse Events as a Measure of Safety and Tolerability of MEDI7352
12 Lead electrocardiogram (including QTc, QRS, PR intervals and ventricular rate)
Number of Participants with Adverse Events as a Measure of Safety and Tolerability of MEDI7352
Vital signs (systolic and diastolic BP), heart rate
Number of Participants with Adverse Events as a Measure of Safety and Tolerability of MEDI7352
MRI
Secondary Outcome Measures
Area under the plasma drug concentration versus time curves for MEDI7352
Area under the plasma drug concentration versus time curves from zero to infinity and to last observation (AUC 0-inf; AUC 0-t).
Maximum observed plasma drug concentration (Cmax) of MEDI7352
Maximum observed plasma drug concentration (Cmax).
Time to maximum observed plasma drug concentration (Tmax) of MEDI7352
Time to maximum observed plasma drug concentration (Tmax).
Terminal plasma elimination half-life (t1/2) of MEDI7352
Terminal plasma elimination half-life (t1/2).
Apparent clearance (CL/F).
Apparent clearance (CL/F).
The presence of anti-drug antibodies (ADAs) to MEDI7352
The incidence of anti-drug antibodies (a measure of the body's immune response to the drug).
Pain Numerical Rating Scale (NRS)
Numerical Rating Scale (NRS)
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale, stiffness subscale and function subscale.
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale, stiffness subscale and function subscale.
Patients' Global Impression of Change Scale (PGIC)
Patients' Global Impression of Change Scale (PGIC)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02508155
Brief Title
A Study of MEDI7352 in Painful Osteoarthritis of the Knee
Official Title
A Randomised, Double-Blind, Placebo-Controlled, Single- and Multiple-Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MEDI7352 in Subjects With Painful Osteoarthritis of the Knee
Study Type
Interventional
2. Study Status
Record Verification Date
April 2021
Overall Recruitment Status
Completed
Study Start Date
November 17, 2015 (Actual)
Primary Completion Date
December 23, 2020 (Actual)
Study Completion Date
December 23, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to assess the safety, drug levels and effects on the body of MEDI7352, in subjects with painful osteoarthritis of the knee.
Detailed Description
An interleaved SAD/MAD Study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of MEDI7352 in subjects with painful osteoarthritis of the knee.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Pain
7. Study Design
Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
132 (Actual)
8. Arms, Groups, and Interventions
Arm Title
MEDI7352 IV
Arm Type
Experimental
Arm Description
Up to 11 cohorts of subjects are planned to be dosed by IV infusion, with single and multiple ascending doses.
Arm Title
IV Placebo
Arm Type
Placebo Comparator
Arm Description
Up to 11 cohorts of subjects are planned to be dosed by IV infusion, with single and multiple ascending doses.
Arm Title
MEDI7352 Subcutaneous Injection
Arm Type
Experimental
Arm Description
1 cohort of subjects is planned to be dosed by subcutaneous injection, one single ascending dose cohort.
Arm Title
Subcutaneous Placebo
Arm Type
Placebo Comparator
Arm Description
1 cohort of subjects is planned to be dosed by subcutaneous injection, one single ascending dose cohort.
Intervention Type
Biological
Intervention Name(s)
MEDI7352 for IV infusion
Intervention Description
MEDI7352 for IV infusion
Intervention Type
Biological
Intervention Name(s)
Placebo for IV infusion
Intervention Description
IV Placebo infusion
Intervention Type
Biological
Intervention Name(s)
MEDI7352 for Subcutaneous Injection
Intervention Description
MEDI7352 for subcutaneous injection
Intervention Type
Biological
Intervention Name(s)
Placebo for Subcutaneous Injection
Intervention Description
Subcutaneous Placebo Injection
Primary Outcome Measure Information:
Title
Number of Participants with Adverse Events as a Measure of Safety and Tolerability of MEDI7352
Description
Adverse events, serious adverse events,
Time Frame
All visits from screening up to 56 days post single dose/84 days post multiple dose
Title
Number of Participants with Adverse Events as a Measure of Safety and Tolerability of MEDI7352
Description
Clinical laboratory assessments (serum chemistry, hematology, urinalysis)
Time Frame
All visits from screening up to 56 days post single dose/84 days post multiple dose
Title
Number of Participants with Adverse Events as a Measure of Safety and Tolerability of MEDI7352
Description
12 Lead electrocardiogram (including QTc, QRS, PR intervals and ventricular rate)
Time Frame
All visits from screening up to 56 days post single dose/84 days post multiple dose
Title
Number of Participants with Adverse Events as a Measure of Safety and Tolerability of MEDI7352
Description
Vital signs (systolic and diastolic BP), heart rate
Time Frame
All visits from screening up to 56 days post single dose/84 days post multiple dose
Title
Number of Participants with Adverse Events as a Measure of Safety and Tolerability of MEDI7352
Description
MRI
Time Frame
At screening and at follow up visit.
Secondary Outcome Measure Information:
Title
Area under the plasma drug concentration versus time curves for MEDI7352
Description
Area under the plasma drug concentration versus time curves from zero to infinity and to last observation (AUC 0-inf; AUC 0-t).
Time Frame
All visits from screening up to 56 days post single dose/84 days post multiple dose
Title
Maximum observed plasma drug concentration (Cmax) of MEDI7352
Description
Maximum observed plasma drug concentration (Cmax).
Time Frame
All visits from screening up to 56 days post single dose/84 days post multiple dose
Title
Time to maximum observed plasma drug concentration (Tmax) of MEDI7352
Description
Time to maximum observed plasma drug concentration (Tmax).
Time Frame
All visits from screening up to 56 days post single dose/84 days post multiple dose
Title
Terminal plasma elimination half-life (t1/2) of MEDI7352
Description
Terminal plasma elimination half-life (t1/2).
Time Frame
All visits from screening up to 56 days post single dose/84 days post multiple dose
Title
Apparent clearance (CL/F).
Description
Apparent clearance (CL/F).
Time Frame
All visits from screening up to 56 days post single dose/84 days post multiple dose
Title
The presence of anti-drug antibodies (ADAs) to MEDI7352
Description
The incidence of anti-drug antibodies (a measure of the body's immune response to the drug).
Time Frame
All visits from screening up to 56 days post single dose/84 days post multiple dose
Title
Pain Numerical Rating Scale (NRS)
Description
Numerical Rating Scale (NRS)
Time Frame
All visits from screening up to 56 days post single dose/84 days post multiple dose
Title
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale, stiffness subscale and function subscale.
Description
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale, stiffness subscale and function subscale.
Time Frame
All visits from screening up to 56 days post single dose/84 days post multiple dose
Title
Patients' Global Impression of Change Scale (PGIC)
Description
Patients' Global Impression of Change Scale (PGIC)
Time Frame
All visits from screening up to 56 days post single dose/84 days post multiple dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male and female subjects with painful osteoarthritis (OA) of the knee. Female subjects must be postmenopausal or surgically sterile.
Body weight between 50kg and 145kg
Willing and able to comply with the requirements of the protocol
Exclusion Criteria:
Current treatment with another biologic therapeutic agent
Current of historical diagnosis of RA
Current diagnosis of an immunological condition that is associated with another form of arthritis in addition to OA, including traumatic arthritis or a seronegative spondyloarthropathy
At risk of destructive arthropathy, including Rapidly Progressive Osteoarthritis (RPOA), osteonecrosis, spontaneous osteonecrosis of the knee, subchondral insufficiency fractures, hip dislocation and pathological fracture
Presence of clinically significant neuropathy or other clinically significant disorder involving abnormal peripheral sensation.
Current serious or unstable clinically important illness.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Bell, MB BCh BAO MRCGP FFPM
Organizational Affiliation
Biokinetics
Official's Role
Principal Investigator
Facility Information:
Facility Name
Research Site
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
Research Site
City
Göteborg
ZIP/Postal Code
413 45
Country
Sweden
Facility Name
Research Site
City
Stockholm
ZIP/Postal Code
141 86
Country
Sweden
Facility Name
Research Site
City
Belfast
ZIP/Postal Code
BT2 7BA
Country
United Kingdom
Facility Name
Research Site
City
London
ZIP/Postal Code
NW10 7EW
Country
United Kingdom
Facility Name
Research Site
City
Manchester
ZIP/Postal Code
M13 9NQ
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
IPD Sharing Time Frame
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
IPD Sharing Access Criteria
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
IPD Sharing URL
https://astrazenecagroup-dt.pharmacm.com/DT/Home
Learn more about this trial
A Study of MEDI7352 in Painful Osteoarthritis of the Knee
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